The conference, "New Directions for Sickle Cell Therapy in the Genome Era" was held at the National Institutes of Health in November, 2003. The participants concluded that "the time is propitious to bring to bear the developing tools and approaches of genomics to develop markedly more effective therapies for sickle cell disease" and as "over 95% of affected individuals are living outside the United States, the application of genomics to sickle cell disease requires a global perspective and involvement." A key recommendation was that "An innovative multidisciplinary Sickle Cell Disease Research Network with a central prospective registry of well phenotyped patients should be established" and that "Features of such a network might include: Respositories of DNA, cell lines, mRNA, and plasma (the latter two from individuals when both symptomatic and asymptomatic), Standardized phenotypes, Open access to materials and data, Longitudinal follow-up and a Clinical trials database." To meet these challenges we propose to establish a clinical core encompassing Medical Centers in Boston, New Haven and Paris, France. The French Center has more that almost 1500 well characterized patients and has partnered before with Boston investigators. The Yale Center brings 150 new pediatric patients to our Clinical Core. Neither of these centers have participated in recent clinical trials in the United States. Our research topics include 1- basic hemoglobin genotyping and erythrocyte phenotyping of all National Sickle Cell Disease Clinical Research Network patients and the transfer of biological samples to a repository for future use by all investigators; 1-a phase I I/I11trial of inhaled nitric oxide for sickle cell vasoocclusive painful episode.